Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant.

BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection. METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays. RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%). CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.

[Major Ionic Characteristics and Factors of Karst Groundwater at Huixian Karst Wetland, China].

To investigate the major ionic chemical characteristics and seasonal variations, 27 groundwater samples were collected from the wet season, flat season, and dry season during 2018-2019 in the Huixian Karst wetland, which is the largest low-altitude karst wetland in China. The single pollution standard index was applied to evaluate the groundwater pollution during different periods, and the major ionic factors of the karst groundwater were analyzed using the statistical analysis method, Gibbs diagram, and ion ratio. The results revealed that the groundwater samples were a weakly alkaline fresh water that were rich in Ca2+ and HCO3-. The average concentrations of the primary ions followed the order of flat season > wet season > dry season; meanwhile, the water quality in the dry season was better than that in the wet and flat seasons. The K+ and NO3- in the karst groundwater were mostly affected by the spatial distributions of the aquifers, and the Mg2+, SO42-, NO2-, NH4+, and TDS were related to the space-season scale. Na+, Ca2+, HCO3-, and Cl- were relatively stable ions in the karst groundwater. The hydrochemical characteristics were primarily determined by carbonate rock dissolution and were found to be the HCO3-Ca type, which accounted for 77.78%, 77.78%, and 88.89% in the wet season, flat season, and dry season, respectively. The karst groundwater was predominantly polluted by SO42-, NO3-, and NO2-; particularly, NO3- exhibited serious pollution points, and SO42- had heavy pollution points in the wet and flat seasons. The chemical composition of the karst groundwater was controlled mostly by water-rock interactions. Ca2+ and HCO3- primarily came from calcite dissolution, and the high concentrations of Mg2+ and SO42- in a few number of points were controlled by dolomite, dolomitic limestone, and pyrite. K+, Na+, SO42-, NO3-, and Cl- partly came from atmospheric precipitation, and Na+ and Cl- partly came from human activities; K+ was related to potash fertilizer, and the main source of NO3- was chemical fertilizer.

Quantitative Assessment of the Association between ABC Polymorphisms and Osteosarcoma Response: a Meta-analysis.

BACKGROUND: ABC proteins are one key type of transport superfamilies which undertake majority of drug transport, which affect the osteosarcoma response to chemotherapeutics. Previous studies have suggested the association between ABC polymorphisms and osteosarcoma response. However, the results of previous studies remain controversial. Therefore, we perform a meta-analysis to get a more precise estimation of this association. The association between ABC polymorphisms and osteosarcoma response was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Three polymorphisms of ABC including ABCB1 rs1128503, ABCC3 rs4148416 and ABCC2 rs717620 polymorphism were investigated. Overall, significant association was observed between ABCC3 rs4148416 polymorphism and osteosarcoma response under allele contrast (T vs. C: OR=1.73, 95%CI=1.09-2.74, P=0.019), homozygote comparison (TT vs. CC: OR=2.00, 95%CI=1.25-3.23, P=0.004), recessive genetic model (TT vs. TC/CC: OR=1.80, 95%CI=1.14-2.84, P=0.011) and dominant genetic model (TT/TC vs. CC: OR=1.70, 95%CI=1.20-2.42, P=0.003). Moreover, significant association was also observed in Caucasian population rather than Asian population for ABCB1 rs1128503 polymorphism. We conclude that ABCC3 rs4148416 polymorphism was significantly associated with poor osteosarcoma response and ABCB1 rs1128503 polymorphism was significantly associated with good osteosarcoma response in Caucasian population rather than Asian population.

Pharmacokinetics of duloxetine hydrochloride enteric-coated tablets in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study.

BACKGROUND: Duloxetine hydrochloride is a balanced selective serotonin and norepinephrine reuptake inhibitor. Despite being widely used for the treatment of major depressive disorder in China, little information is available on the pharmacokinetic (PK) properties of duloxetine in Chinese subjects. OBJECTIVES: This study was designed to determine the concentration of duloxetine in human plasma and to compare the PK properties of duloxetine after administration of single and multiple doses of duloxetine in healthy Chinese volunteers. METHODS: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining the concentration of duloxetine in human plasma was developed and applied to this single-center, open-label, single- and multiple-dose PK study. Subjects were randomized to receive a single dose of 30, 60, or 90 mg of duloxetine. Those who received the 30-mg dose continued on to the multiple-dose phase and received 30 mg twice daily for 7 days. In the single-dose phase, sequential blood samples were collected from 0 to 60 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration on days 4, 5, 6, and 7 to determine the C(ssmin) of duloxetine; on day 7, samples were collected from 0 to 60 hours after drug administration. The PK parameters that were calculated included C(max), T(max), t(1/2), AUC(0-t) AUC(0-infinity), CL, V(d), C(ssmax), C(ssmin), C(ssav), AUC(ss), AUC(ss(0-t)), and C(max):C(min) ratio. All values were expressed as mean (SD). Tolerability was assessed throughout the study. RESULTS: The LC-MS/MS method was developed and validated. The standard calibration curve was linear in the concentration range from 0.89 to 106.8 ng/mL; the correlation coefficient was >0.995. The methodologic recovery and extraction recovery ranged from 87.22% to 113.75% and 72.81% to 89.96%, respectively. Both the intraday and interday relative SDs were <11%. Thirty Chinese subjects (3 groups of 10 subjects [5 men, 5 women] each) were enrolled in the single-dose phase of the PK study. The mean (SD) age of the subjects was 23.2 (1.8) years (range, 21-25 years); their mean (SD) weight was 61.0 (7.7) kg (range, 52-80 kg) and height was 169.0 (7.1) cm (range, 155-180 cm). The main PK parameters for duloxetine after administration of a single oral dose of 30, 60, and 90 mg were as follows: C(max) = 22.46 (15.15), 44.40 (17.18), and 60.78 (27.84) ng/mL, respectively; AUC(0-60) = 328.64 (203.64), 696.04 (337.82), and 1219.33 (598.29) ng/mL . h(-1); AUC(0-infinity)) = 359.68 (201.01), 733.82 (343.40), and 1280.51 (644.81) ng/mL . h(-1); T(max) = 6.83 (1.99), 6.10 (1.29), and 6.60 (1.58) hours; t1/2 = 12.95 (3.64), 12.81 (2.31), and 11.66 (2.06) hours; CL = 107.90 (53.05), 98.41 (41.98), and 109.58 (52.74) L/hour; and V(d) = 2518.88 (1707.71), 1879.74 (999.09), and 1858.47 (1203.69) L. The 10 subjects who received the 30-mg dose in the single-dose phase continued on to the multiple-dose phase and received 30 mg of duloxetine twice daily for 7 days. Mean (SD) values for the main PK parameters for duloxetine after administration of multiple doses were as follows: C(ssmax) = 47.33 (16.95) ng/mL; C(ssmm) = 27.92 (9.46) ng/mL; AUC(ss(0-t)) = 407.25 (125.94) ng/mL . h(-1); C(ssav) = 33.94 (13.00) ng/mL; T(max) = 6.36 (0.92) hours; t(1/2) = 11.19 (1.98) hours; CL = 83.12 (28.75) L/hour; and V(d) = 1359.01 (590.06) L. CONCLUSIONS: In these healthy Chinese subjects, AUC and Cmax increased proportionally with the dose, whereas t(1/2) was independent of the dose. Linear PK properties were found at doses of 30 to 90 mg. No statistically significant differences were observed between the PK parameters for the subjects in the multiple-dose phase (t(1/2), CL, V(d)) and those for subjects in the single-dose phase. The AUC and C(max) were greater after administration of multiple doses than after administration of a single dose, suggesting du-loxetine accumulation with multiple-dose administration of 30 mg.